Conformational changes in amyloid-beta (12-28) alloforms studied using action-FRET, IMS and molecular dynamics simulations

Chemical Science
Steven DalyPhilippe Dugourd

Abstract

Small oligomers of the amyloid beta protein (Aβ) have been implicated as the neurotoxic agent leading to Alzheimer's disease, and in particular mutations in the hydrophobic core region comprising amino acids L17 to A21 have a large influence on the propensity for aggregate formation. It has been shown that the F19P alloform of Aβ forms small aggregates, but does not proceed to form large fibrils and plaques. In order to understand the origin of this behavior, the gas phase conformations for the different charge states of the wild-type 12-28 fragment of the amyloid beta and its F19P alloform were studied by a combination of action-FRET, ion-mobility spectrometry (IMS) and molecular dynamics simulations. Comparison of the experimental and theoretical action-FRET efficiencies and collision cross sections allowed the determination of the lowest energy conformational family for each alloform and charge state. For both alloforms, it was found that there is a change from globular to helical structure between the 3+ and 4+ charge states. Additional protonation to give 5+ and 6+ charge states caused unfolding of this helical motif, with the wild alloform showing β-turn like motifs and the F19P alloform random coil motifs. The presence o...Continue Reading

References

Nov 1, 1991·Biophysical Journal·P E FraserD A Kirschner
Nov 1, 1968·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·E D Eanes, G G Glenner
Mar 1, 1994·Journal of Neurochemistry·P E FraserD R McLachlan
Mar 29, 2001·Physiological Reviews·D J Selkoe
Sep 5, 2002·Journal of Neuroscience Research·Marina D KirkitadzeDavid B Teplow
Dec 10, 2002·Annual Review of Physical Chemistry·Gregory D Scholes
Jul 4, 2003·The Journal of Biological Chemistry·Gal BitanDavid B Teplow
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jun 17, 2004·Journal of the American Chemical Society·Motoya KohtaniMartin F Jarrold
Sep 29, 2004·Current Opinion in Chemical Biology·Robert H H van den Heuvel, Albert J R Heck
Feb 17, 2005·Journal of the American Chemical Society·Summer L BernsteinMichael T Bowers
Mar 31, 2005·Journal of the American Chemical Society·Philippe DugourdMartin F Jarrold
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Nov 1, 2005·Analytical Chemistry·Xun Cheng, Richard B van Breemen
Aug 26, 2006·Journal of Molecular Biology·Andrij Baumketner, Joan-Emma Shea
Aug 29, 2006·Current Opinion in Chemical Biology·Brandon T Ruotolo, Carol V Robinson
Sep 20, 2006·Accounts of Chemical Research·David B TeplowH Eugene Stanley
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Apr 24, 2009·Journal of the American Chemical Society·Megan M MurrayMichael T Bowers
Oct 23, 2010·Journal of the American Chemical Society·Francis O TalbotRebecca A Jockusch
Apr 29, 2011·Journal of the American Chemical Society·Francis CanonPhilippe Dugourd
Sep 18, 2012·The Journal of Physical Chemistry. B·Paulami MandalAndreas Barth
Dec 25, 2012·Biophysical Journal·Yu-Shan Lin, Vijay S Pande
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl

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Citations

Jul 20, 2018·Chemistry : a European Journal·Mathieu LalandeJean-Christophe Poully
Nov 28, 2017·Biopolymers·Andrea PizziPierangelo Metrangolo
Sep 29, 2018·Rapid Communications in Mass Spectrometry : RCM·Tara Pukala
Mar 14, 2019·Chemical Communications : Chem Comm·Rui GengWen Zhang
Apr 13, 2019·Chemical Communications : Chem Comm·Lin LiuJinyu Li
Mar 25, 2017·Physical Chemistry Chemical Physics : PCCP·Alexander KuleszaPhilippe Dugourd
Oct 3, 2015·The Review of Scientific Instruments·Anne-Laure SimonPhilippe Dugourd
Jun 10, 2018·Rapid Communications in Mass Spectrometry : RCM·Chang Min ChoiFabien Chirot
Mar 15, 2016·Physical Chemistry Chemical Physics : PCCP·Alexander KuleszaPhilippe Dugourd
Nov 3, 2016·Chemistry : a European Journal·Arianna BertolaniPierangelo Metrangolo
Jan 10, 2016·The Journal of Chemical Physics·Caroline SeaibyThomas R Rizzo
Aug 11, 2016·Journal of the American Society for Mass Spectrometry·Steven DalyPhilippe Dugourd
Jul 30, 2017·Journal of the American Society for Mass Spectrometry·Mathilde BouakilPhilippe Dugourd
Aug 16, 2021·Mass Spectrometry Reviews·František Tureček
Jan 13, 2016·The Journal of Physical Chemistry. B·Chang Min ChoiPhilippe Dugourd
Aug 20, 2019·Chemical Reviews·Satchin SoorkiaGilles Grégoire
May 2, 2018·Journal of Chemical Theory and Computation·Ioana-Mariuca IlieWim J Briels
Dec 31, 2016·Analytical Chemistry·Jody C MayJohn A McLean
Jun 20, 2020·The Journal of Physical Chemistry. B·Sneha MenonPayel Das

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Methods Mentioned

BETA
NMR
FRET
irradiating

Software Mentioned

Gromacs
AMBER99

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